Our proposed research includes the synthesis and pharmacological evaluation of a number of conformationally restricted analogs of metaraminol and alpha- methyl-m-tyramine. These analogs along with the ephedrine analogs we have available, will be used to gain further insight into the conformational requirements for (a) pharmacological receptors, (b) the depletion of endogenous catecholamines from the neurone, and (c) inhibition of neuronal uptake sites in the peripheral and central adrenergic nervous systems. The information gained as to the conformational requirements for the uptake of catecholamines may be useful in providing drugs that can act as antidepressants or useful in the treatment of parkinsonism. Certain of the conformationally restricted analogs of metaraminol should possess potent alpha-adrenergic agonist activity and possibly could serve as selective nasal decongestants or antihypotensive drugs. Since some of the conformationally restricted amines may act as false neurotransmitters, they could prove to be of value as antihypertensives.